Eli Lilly and Company announced positive topline results from its Phase 3 TRANSCEND-T2D-1 clinical trial evaluating retatrutide, an investigational triple hormone receptor agonist, for the treatment of adults with type 2 diabetes. The therapy, designed as an adjunct to diet and exercise, met the primary and all key secondary endpoints, demonstrating significant improvements in both blood sugar control and weight loss.
In the trial, retatrutide reduced A1C levels by up to 2.0% over 40 weeks, compared to a 0.8% reduction with placebo. Participants receiving the highest 12 mg dose achieved an average weight loss of 36.6 pounds, equivalent to 16.8% of body weight. The study also found that weight loss continued throughout the 40-week treatment period, with no observed plateau.
The trial enrolled adults with type 2 diabetes who had inadequate glycemic control through diet and exercise alone, with an average disease duration of 2.5 years. Retatrutide demonstrated superiority over placebo using both efficacy and treatment-regimen estimands.
Beyond glycemic control and weight reduction, the drug showed improvements in cardiovascular risk markers, including non-HDL cholesterol, triglycerides, and systolic blood pressure. The safety profile was consistent with other incretin-based therapies, with the most common adverse events including nausea, diarrhea, and vomiting, primarily occurring during dose escalation. Discontinuation rates due to adverse events ranged from 2.2% to 5.1% across dosing groups, compared to 0% in the placebo group.
Retatrutide is a first-in-class therapy targeting three hormone receptors, GIP, GLP-1, and glucagon, positioning it as a next-generation treatment in the increasingly competitive diabetes and obesity market.
KEY QUOTE:
“For many people with type 2 diabetes, it is a struggle to achieve both A1C control and weight loss, since obesity has historically been harder to treat for those with type 2 diabetes. With triple agonist retatrutide, we set out to make a molecule that could help patients achieve substantial A1C reduction and weight loss. These results support the remarkable potential of this novel molecule for people living with type 2 diabetes, with up to 2% A1C improvement and nearly 17% weight loss in 40 weeks of treatment.”
Kenneth Custer, Ph.D., Executive Vice President and President, Lilly Cardiometabolic Health
